Mwendo by Ambrosia

POSSIBLY EFFECTIVE

• Common cold. Oral andrographis, taken alone or as part of a specific combination product (Kan Jang, Swedish Herbal Institute) also containing eleuthero, seems to improve symptoms of the common cold. It is unclear if oral andrographis is beneficial for preventing the common cold. Details: Most clinical research shows that taking andrographis alone or as part of a combination herbal supplement improves cold symptoms (2744,2773,2774,5784,10795,12380,12381,98222). Taking a specific combination product (Kan Jang, Swedish Herbal Institute) containing andrographis extract, standardized to andrographolides 4-5.6 mg, and eleuthero three times daily seems to improve symptoms of the common cold when started within 72 hours of symptom onset. Some symptoms can improve after 2 days of treatment, but it typically takes 4-5 days of treatment for maximal symptom relief (2744,2773,2774,5784,10795,12380). This combination also seems to relieve cold symptoms better than echinacea or placebo in children (12381). Other clinical research shows that taking a specific andrographis extract (KalmCold) 200 mg daily for 5 days reduces cold symptoms by approximately two-fold and increases the number of patients who respond to treatment when compared with placebo (31222). Preliminary clinical research shows that taking andrographis (Kan Jang, Swedish Herbal Institute) prophylactically might decrease the risk of developing a cold by about 50% after 2 months of continuous treatment (2772); however, more evidence is needed to confirm these results.
• Osteoarthritis. Oral andrographis extract has been evaluated for the treatment of osteoarthritis, with promising results. Details: In patients with mild to moderate osteoarthritis of the knee, clinical research shows that taking a specific brand of andrographis extract (ParActin, HP Ingredients) 300 mg and 600 mg daily for 12 weeks reduces pain and stiffness by approximately 40% and 46%, respectively, compared with changes of less than 10% with placebo (101116).
• Tonsillopharyngitis. Oral andrographis has been evaluated for the management of fever and sore throat associated with tonsillopharyngitis, with promising results. Details: Some clinical research shows that andrographis 6 grams daily is comparable to acetaminophen for reducing fever and sore throat associated with tonsillopharyngitis after 3 and 7 days of treatment (2748).
• Ulcerative colitis. Oral andrographis extract has been evaluated for the management of ulcerative colitis symptoms, with promising results. Details: Some clinical research shows that taking andrographis extract 1200-1800 mg daily for 8 weeks reduces symptoms of mild to moderate ulcerative colitis, but does not affect remission rates, when compared with placebo (31231). Additional clinical research also shows that taking andrographis extract 1200 mg daily for 8 weeks is as effective as mesalamine for reducing symptoms in patients with ulcerative colitis (31223).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acute bronchitis. Although there has been interest in using oral andrographis for acute bronchitis, there is insufficient reliable information about the clinical effects of andrographis for this purpose.
• Cognitive impairment. Oral andrographis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in a small number of patients with mild cognitive impairment shows that taking a combination product (Adaptra Forte, Europharma USA) containing andrographis extract 400 mg, standardized to andrographolides 40 mg, and ashwagandha extract 150 mg twice daily for 4 weeks modestly improves some measures of concentration and sleep quality when compared with placebo (104822).
• Coronavirus disease 2019 (COVID-19). It is unclear if oral andrographis is beneficial in mild to moderate COVID-19. Details: A moderate-sized clinical study in adults with mild to moderate COVID-19 receiving standard of care conducted in India shows that taking andrographis raw plant part extract 200 mg twice daily for 14 days improves the time to clinical improvement by 2-points on the World Health Organization (WHO) scale to about 4 days compared with about 6 days in the control group (112920). However, the interpretation of this finding is limited by unbalanced groups with sicker patients in the control group. Additionally, a large observational study conducted in Thailand in unvaccinated hospitalized adults with mild COVID-19 suggests that taking andrographis, dosed as andrographolide 60 mg, three times daily for 5 days is not associated with a decrease in the risk of developing pneumonia when compared with standard of care (112919).
• Diabetes. Oral andrographis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in adults with type 2 diabetes who are taking metformin 1000 mg daily shows that taking a combination product containing andrographis and Syzygium polyanthum leaf extracts, 900 mg daily for 8 weeks, does not improve fasting blood glucose levels, glycated hemoglobin (HbA1c), blood pressure, or blood lipid levels when compared with placebo (101117).
• Familial Mediterranean fever. Oral andrographis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in children 3-15 years of age shows that taking a combination product (ImmunoGuard, Inspired Nutritionals) containing andrographis 16 mg, eleuthero, schisandra, and licorice daily for 1 month reduces the duration, frequency, and severity of attacks of familial Mediterranean fever (12382).
• Hypertriglyceridemia. It is unclear if oral andrographis is beneficial in patients with hypertriglyceridemia. Details: A small clinical study in adults with hypertriglyceridemia shows that taking andrographis, standardized to contain andrographolide 119.64-120.36 mg, by mouth daily for 8 weeks decreases triglycerides by 42 mg/dL, demonstrating comparable effects to gemfibrozil. However, compared to baseline, total cholesterol was increased by 15 mg/dL and low-density lipoprotein (LDL) cholesterol was increased by 21 mg/dL, suggesting that the benefits of lower triglycerides may be offset by elevations in other lipid levels. Taking a lower daily dose of andrographis, standardized to contain andrographolide 71.64-72.36 mg, does not seem to affect lipid levels (91839).
• Impaired glucose tolerance (prediabetes). It is unclear if oral andrographis is beneficial in patients with prediabetes. Details: A small crossover clinical study in adults with prediabetes conducted in Indonesia shows that taking andrographis 550 mg for 14 days increases glucagon-like peptide 1 (GLP-1) levels but does not statistically improve measures of insulin resistance (i.e., fasting insulin, fasting glucose, 2-hour postprandial glucose, 2-hour postprandial insulin, homeostatic model assessment for insulin resistance [HOMA-IR]) when compared with placebo (112918). However, it is unclear whether this improvement is clinically significant. In addition, the frequency of andrographis dosing is unclear.
• Influenza. Oral andrographis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that patients with influenza who take a specific product (Kan Jang, Swedish Herbal Institute) containing andrographis extract, standardized to andrographolides 4-5.6 mg, and eleuthero three times daily for 3-5 days have more rapid symptom relief when compared with patients taking amantadine. Taking this combination product also seems to reduce the risk of post-influenza complications such as rhinosinusitis or bronchitis when compared with amantadine (10441).
• Migraine headache. Oral andrographis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Research has evaluated a combination product (Vivinor, Brain Therapeutics; Partena, FB Health) containing andrographis 100 mg, magnesium 281 mg, riboflavin 5 mg, feverfew 150 mg, and coenzyme Q10 20 mg. A nonblinded, clinical study in patients with episodic migraines shows that taking 1-2 tablets of this product daily for 3 months decreases monthly average migraine days, migraine severity, and the number of days an acute migraine medication is used when compared with baseline. In the third month of treatment, 57% of patients had at least a 50% reduction in average migraine days (107473). The validity of this study is limited by the lack of randomization and placebo-control; additionally, it is unclear if any effects are due to andrographis, the other ingredients, or the combination.
• Multiple sclerosis (MS). It is unclear if oral andrographis is beneficial in patients with MS. Details: A small clinical study in patients with relapsing-remitting MS currently receiving interferon-beta shows that taking andrographis dried extract (Innobioscience Spa) 170 mg, standardized to contain andrographolides 85 mg, twice daily for 12 months decreases fatigue by 44%, but does not affect relapse rate or disability, when compared with placebo (91838). Another small clinical study of patients with primary or secondary, but not active, progressive MS shows that taking andrographolide, a constituent of andrographis, 140 mg twice daily for 24 months slows the progression of disability when compared with placebo (104821).
• Rheumatoid arthritis (RA). It is unclear if oral andrographis is beneficial in patients with RA. Details: Preliminary clinical research shows that taking andrographis extract 90 mg daily for 14 weeks reduces symptoms of RA when compared to baseline, but not when compared with placebo (31220).
• Rhinosinusitis. Although there has been interest in using oral andrographis for rhinosinusitis, there is insufficient reliable information about the clinical effects of andrographis for this purpose.
• Upper respiratory tract infection (URTI). Oral andrographis has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in adults with uncomplicated URTI shows that a specific combination product (Kan Jang, Swedish Herbal Institute) containing andrographis 195 mg and eleuthero root 11.4 mg per capsule, taken as two capsules three times daily for 5 days, reduces the median number of sick leave days to 2 days, compared with 3 days in the placebo group. It also increases the total number of recovered patients on day 3 to 75%, compared with 55% of those taking placebo (107471). More evidence is needed to rate andrographis for these uses.

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POSSIBLY EFFECTIVE

• Obesity. Several small clinical studies suggest that oral Cissus quadrangularis extract, taken with or without other ingredients, can decrease body weight in those who are overweight or obese. Details: Two small clinical studies in adults with overweight or obesity shows that taking a specific Cissus quadrangularis extract standardized to 2.5% keto-steroids and 15% soluble plant fiber (CQR-300, Gateway Health Alliance) 300 mg daily for 6-8 weeks with a reduced calorie diet decreases body weight by around 4% to 11%, compared with a 0% to 3% reduction with reduced calorie dieting alone (15609,93637). Other small clinical studies in patients with overweight or obesity shows that taking 300 mg of this product daily for 8-10 weeks without following any specific diet decreases body weight by about 8% to 9%, compared with about 2% in those taking placebo (16457,99257). Taking this product also appears to reduce body fat by about 13%, compared with no decrease in those taking placebo (99257). However, most of these studies are of moderate to low quality, and all are short-term, limiting the reliability of the findings. Cissus quadrangularis has also been evaluated in combination with other ingredients. Several small clinical studies show that taking a specific combination product containing Cissus quadrangularis (standardized to 2.5% keto-steroids and 15% soluble plant fiber), green tea, soy, chromium, selenium, and B-vitamins (Cylaris, Iovate Health Sciences International) 1028 mg daily, taken in single or divided doses, for 8 weeks reduces weight by around 7% or 6.6 kg when used alone. When used with a reduced calorie diet, body weight is reduced by 8.5% or 8.1 kg (15608,15609,95921). It is unclear if these findings are due to Cissus quadrangularis, other ingredients, or the combination.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Asthma. Although there has been interest in using oral Cissus quadrangularis for asthma, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
• Cancer. Although there has been interest in using oral Cissus quadrangularis for cancer, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
• Diabetes. Although there has been interest in using oral Cissus quadrangularis for diabetes, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
• Epilepsy. Although there has been interest in using oral Cissus quadrangularis for epilepsy, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
• Fractures. Several small, low-quality clinical trials suggest that oral Cissus quadrangularis may accelerate the healing of various types of fractures and reduce pain and swelling. Details: Two small clinical studies in patients with jaw fractures in India show that taking powdered Cissus quadrangularis whole herb 500 mg three times daily for 6 weeks or a different Cissus quadrangularis preparation containing dried stem 600 mg twice daily for 8 weeks reduces pain, swelling, and healing time when compared with placebo (93634,95923). In patients with single, simple bone fractures, a small clinical study in India shows that taking an Ayurvedic preparation of crude, powdered Cissus quadrangularis (Asthishrunkhala churna), 10 grams divided into three doses daily for 30 days, accelerates bone healing and reduces analgesic requirements when compared with placebo (95921). Another small clinical trial in patients with distal radius fractures shows that taking the same Ayurvedic preparation orally, 3-4 grams twice daily for 6 weeks, with or without a topical preparation of Cissus quadrangularis, 15 grams applied once daily for 2 weeks, seems to decrease subjective measures of pain and swelling when compared to baseline (95922). The validity of this finding is limited by the lack of a comparator group. In patients with a fracture of the long bones of the leg, a very small clinical study in India shows that taking a specific Cissus quadrangularis extract (Calzbone, Verdure Sciences) 250 mg orally three times daily decreases the average fracture healing time from 16-20 weeks to 12-14 weeks (43216). Cissus quadrangularis has also been evaluated in combination with other ingredients. A small, open label trial in India among patients with jaw fractures shows that taking Cissus quadrangularis 500 mg and Dalbergia sissoo 400 mg twice daily for 4 weeks improves bite force restoration when compared with placebo, but not when compared with teriparatide. Improvements in pain, fracture site mobility, and bone healing were lacking in all groups (112139). The study may have been inadequately powered to detect differences between the groups, and it is unclear if these findings are due to Cissus quadrangularis, Dalbergia sissoo, or the combination.
• Gout. Although there has been interest in using oral Cissus quadrangularis for gout, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
• Hemorrhoids. Small clinical studies suggest that oral or topical Cissus quadrangularis extracts may not improve symptoms of hemorrhoids. Details: Several small clinical studies in patients with acute, symptomatic hemorrhoids show that taking Cissus quadrangularis extract as either 100 mg daily for 1 week, 180 mg daily for 2 weeks, or 1 gram three times daily for 3 days followed by 1 gram twice daily for 4 days, does not improve symptoms of hemorrhoids when compared with placebo (43204,95921). Using a topical preparation of Cissus quadrangularis extract three times daily for 1 week also seems to be no better than placebo (95921). Another small clinical study in this population shows that rectal administration of a suppository containing Cissus quadrangularis extract 1% and Amcella paniculata extract 1% twice daily for 7 days results in similar improvements in anal pain, bleeding, and prolapse size when compared with a commercial suppository containing hydrocortisone 5 mg and cinchocaine 5 mg (108548). It is unclear if these findings are due to Cissus quadrangularis, Amcella paniculate, or the combination.
• Hyperlipidemia. Although there has been interest in using oral Cissus quadrangularis for hyperlipidemia there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
• Joint pain. It is unclear if oral Cissus quadrangularis is beneficial in patients with joint pain. Details: A small clinical study in males with exercise-related chronic joint pain shows that taking two 800 mg capsules of a specific Cissus quadrangularis product (SuperCissus, USPlabs) twice daily for 8 weeks decreases pain by 31% and stiffness by 23% when compared to baseline (93633). The validity of these findings is limited by the lack of a comparator group.
• Metabolic syndrome. Although there has been interest in using oral Cissus quadrangularis for metabolic syndrome, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
• Muscle strength. Although there has been interest in using oral Cissus quadrangularis to improve muscle strength, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
• Osteopenia. It is unclear if oral Cissus quadrangularis is beneficial for osteopenia. Details: A moderate-sized clinical trial in Thailand among postmenopausal patients with osteopenia shows that taking Cissus quadrangularis 1200 or 1600 mg daily for 24 weeks does not improve bone mineral density (BMD) when compared with placebo. However, Cissus quadrangularis does seem to improve markers of bone turnover, suggesting that longer-term use might lead to improvements in BMD (112140). Also, a small clinical study in patients with low BMD shows that taking a combination of Cissus quadrangularis, ashwagandha, and holy basil once daily for 6 months seems to improve BMD, T-score, and Z-score when compared with placebo (43217). However, it is unclear if these findings are due to Cissus quadrangularis, other ingredients, or the combination.
• Osteoporosis. Although there has been interest in using oral Cissus quadrangularis for osteoporosis, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
• Peptic ulcers. Although there has been interest in using oral Cissus quadrangularis for peptic ulcers, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
• Rheumatoid arthritis (RA). Although there has been interest in using oral Cissus quadrangularis for RA, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose.
• Wound healing. Although there has been interest in using topical Cissus quadrangularis for wound healing, there is insufficient reliable information about the clinical effects of Cissus quadrangularis for this purpose. More evidence is needed to rate Cissus quadrangularis for these uses.

(Read more about CISSUS QUADRANGULARIS)

POSSIBLY EFFECTIVE

• Aging skin. Oral collagen peptides seem to improve skin hydration and elasticity in older adults. However, it is unclear if any improvements related to wrinkles are cosmetically important. Details: Meta-analyses of the available research, as well as multiple individual clinical studies, show that collagen peptide products, taken in doses of 372 mg to 12 grams daily for 4-12 weeks, improve skin hydration and elasticity in older adults. Studied products include Peptan-F or Peptan-P (Rousselot), Wellnex (Nitta Gelatin), Gold Collagen Active (Minerva Research Labs), VERISOL (Gelita AG), and Nippi peptide FCP-EX (Nippi/Shizuoka) (97632,100703,101597,104647,107460,112457). Pooled study results also suggest that hydrolyzed collagen sourced from fish improves skin hydration and elasticity, while collagen peptides originating from chickens seems to modestly improve skin elasticity but not hydration. Collagen peptides derived from bovine do not seem to improve skin hydration or elasticity (112457). Despite research showing improvement in skin hydration and elasticity, it is unclear if collagen peptides reduce skin wrinkles to a cosmetically significant degree, as most studies have not evaluated this outcome. In one clinical study, taking a freshwater fish-derived collagen peptide (Vinh Wellness Collagen, Vinh Hoan Corporation) 10 grams every morning reduced wrinkle count in the nasolabial region of the right side, but not the left side, of the face by 24% when compared with placebo. Collagen peptides did not improve participant-reported measures of wrinkles, elasticity, hydration, and others, when compared with placebo (104639). Another clinical study shows that taking a specific fish scale-derived collagen peptide (Wellnex, Nitta Gelatin) with either a high or low ratio of prolyl-hydroxyproline and hydroxylpropyl-glycine as 5 grams orally daily for 8 weeks modestly improves wrinkle depth and roughness, but not wrinkle volume, when compared with placebo. The product with a high ratio of dipeptides had a larger effect (97632). Also, one clinical study shows that taking a specific product containing porcine collagen type I peptides (VERISOL, Gelita AG) 2.5 grams daily for 8 weeks reduces eye wrinkle volume by 20% when compared with placebo (101648). Two similar moderate-size clinical studies in middle-aged adults with crow's feet wrinkles and dry skin show that taking specific low-molecular-weight fish-derived collagen peptide products (Geltech Co.; CPNS) at doses of 2000 mg or 1650 mg, respectively, daily for 12 weeks improves eye wrinkles, skin hydration, and elasticity when compared with placebo (110729,110730). While investigator satisfaction scores regarding wrinkle reduction were modestly improved, participant satisfaction was not improved (110729). Small clinical studies have shown contradictory findings when collagen peptides are taken in combination with other ingredients. In one clinical trial, a specific drink (Diva Luxe) providing fish collagen peptides 5.5 grams plus Chenopodium formosanum extract 1 gram daily for 8 weeks improved some measures of skin brightness and hydration, but not wrinkles and crow's feet, when compared with placebo (104646). Another small clinical study shows that taking collagen peptides 4 grams daily in combination with coenzyme Q10 50 mg, vitamin C, vitamin A, and biotin for 12 weeks reduces wrinkles and improves skin smoothness by a small amount when compared with placebo. However, there was no difference in skin elasticity or hydration (104638). A clinical study in older females shows that taking collagen peptides 9 grams in combination with zinc and vitamins A, C, and E daily for 90 days increases stratum corneum water content and skin viscoelasticity when compared with placebo. However, it is unclear if the improvement from baseline differed between groups. Small improvements in dermal echogenicity, wrinkles, or skin pores were noted in some facial regions, but the lack of statistical comparison to placebo limits the validity of these findings (107464). Some small clinical studies have shown mixed effects with low doses of collagen peptides from preliminary clinical research using BioCell Collagen (BioCell Technology, LLC) or Celergen (Laboratories-Dom) (28681,97930). It is unclear if any improvements from these studies are due to collagen peptides, other ingredients, or the combinations. Topical application of collagen peptides has been minimally evaluated. A very small observational study in older adults has found that application of a carbopol gel containing collagen peptides 1% to the periorbital area twice daily for 8 weeks is associated with increased skin hydration and elasticity and reduced transepidermal water loss, skin roughness, and wrinkles when compared with baseline (107459). The validity of these findings is limited by poor study methodology, lack of statistical comparison to baseline, and lack of a comparator group.
• Dry skin. Oral collagen peptides seem to improve skin hydration and elasticity in adults with dry skin. However, their effect on other measures of dry skin is unclear. Details: A meta-analysis of 19 clinical studies, along with several small and moderate-sized individual studies, some of which are included in the meta-analysis, show that taking collagen peptides 372 mg to 12 grams daily for 4-12 weeks improves skin hydration and elasticity when compared with placebo in healthy adults (107461,110729,110730,112457,112458). Some studies show that collagen peptides improve skin roughness (107461), decrease peeling (110729,110730), and increase stratum corneum and epidermis water content (107462) but not skin gloss (107461) or elasticity (107462). Some research shows that collagen peptides reduce transepidermal water loss (107462), while another study shows no change (107461). Subgroup analysis of the meta-analysis suggests that hydrolyzed collagen sourced from fish improves skin hydration and elasticity the most, while collagen peptides originating from chicken seem to modestly improve skin elasticity but not hydration. Collagen peptides from bovine do not seem to improve skin hydration or elasticity (112457). Studied products include FCP-Z (Nippi Co., Ltd), Geltech Co., CPNS, and GPVGPS Collagen (Daehan Chemtech) (107462,110729,110730,112458). Collagen peptides have also been evaluated in combination with other ingredients. A small clinical study in healthy adults with low skin moisture shows that drinking 30 mL of a beverage containing fish scale-derived collagen peptides 10 grams and ornithine 400 mg (FUJIFILM) daily for 8 weeks does not improve skin moisture but seems to improve skin elasticity and reduce water loss when compared with placebo (101607). Another very small clinical study in a mixed population of patients with dry skin and mild atopic dermatitis shows that twice daily application of an emollient containing collagen peptides, soluble proteoglycan, and hyaluronic acid for 4 weeks reduces itching severity from moderate at baseline to mild or almost none. Transepidermal water loss and skin hydration also improved when compared to baseline (107465). The validity of these findings is limited by the lack of a comparator group. Both of these studies are limited by their small size, and it is unclear if any improvements are due to collagen peptides, other ingredients, or the combination.

POSSIBLY INEFFECTIVE

• Muscle strength. Most research suggests that oral collagen peptides do not improve leg strength. However, they may improve hand-grip strength and fat-free mass. Details: Small clinical studies in healthy male and female athletes or non-athletes undergoing resistance or other training show that taking collagen peptides 15-30 grams daily or after training sessions for up to 15 weeks, with or without vitamin C, does not improve leg strength (i.e. squat strength, knee extension, or flexor strength) when compared with placebo (101608,104641,107457,110668,110669). Similarly, 2 very small clinical studies in healthy adults show that taking a specific oral collagen peptide product (Bodybalance, Gelita AG) 5-15 grams daily while completing a resistance training program for 14-15 weeks increases patellar tendon cross-sectional area but does not improve most measures of tendinous tissue remodeling including patellar tendon size, vastus lateralis aponeurosis size, patellar tendon mechanical properties, tendon stiffness, maximal knee extension strength, or rectus femoris muscle cross-sectional area when compared with placebo (112452,112454). However, a small clinical study with the same product in untrained females aged 18-50 years shows that taking 15 grams daily in addition to resistance training three times weekly for 12 weeks improves hand-grip strength when compared with resistance training and placebo (101608). In untrained males aged 30-60 years, taking the same dose of this collagen peptide product along with resistance training for 12 weeks improves fat-free mass by 3 kg, compared with 2 kg with resistance training and placebo. A post-hoc exploratory analysis suggests that the effects seen in males are similar to those seen with whey protein (107457).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there has been interest in using oral collagen peptides for acne, there is insufficient reliable information about the clinical effects of collagen peptides for this condition.
• Androgenic alopecia. Oral collagen peptides have only been evaluated in combination with other ingredients, their effect when used alone is unclear. Details: A moderate-sized clinical study in adults with androgenic alopecia or telogen effluvium shows that taking a combination product containing hydrolyzed collagen 300 mg, taurine, cysteine, methionine, iron, and selenium (GFM Oral, Cantabria Labs) daily along with conventional therapy, consisting primarily of finasteride or minoxidil, for 12 weeks improves hair loss when compared with conventional therapy alone (111636). It is unclear if this effect is due to collagen peptides, other ingredients, or the combination.
• Athletic performance. It is unclear if oral collagen peptides improve performance in most athletes. Details: In recreationally active female runners undergoing resistance and endurance training 3 times weekly, clinical research shows that taking collagen peptides 7.5 grams twice daily for 12 weeks increases running distance by approximately 1,034 meters, compared with an increase of 703 meters in those taking placebo, although there was no effect on speed (104641). A clinical study in healthy young male athletes undergoing heavy strength and power training shows that taking collagen peptides 20 grams and vitamin C 50 mg daily for 3 weeks improves squat performance and countermovement jump performance when compared with placebo. However, removal of a single outlier negated the statistical significance of most of these findings (107456). Also, it is unclear if any improvements from this study are due to collagen peptides, vitamin C, or the combination.
• Atopic dermatitis (eczema). It is unclear if oral or topical collagen peptides are beneficial for improving the severity of eczema. Details: A small clinical study in patients with atopic dermatitis shows that taking a porcine skin-derived collagen peptide with a high ratio of tripeptides with glycine-X-Y sequences, 3.9 grams daily for 12 weeks, improves symptoms and severity of eczema when compared to baseline. There was no improvement in the group taking the same dose of porcine skin-derived collagen peptide without the high ratio of tripeptides (101605). Another very small clinical study in a mixed population of patients with atopic dermatitis and dry skin shows that twice daily application of an emollient containing collagen peptides, soluble proteoglycan, and hyaluronic acid for 4 weeks reduces itching severity from moderate at baseline to mild or almost none. Transepidermal water loss and skin hydration also improved when compared to baseline (107465). It is unclear if any improvements are due to collagen peptides, the other ingredients, or the combination. Both of these studies are limited by their small size and lack of comparator groups.
• Burns. Some preliminary clinical research suggests that oral collagen peptides might reduce the time needed for burn healing. Details: In male patients with 20% to 30% body surface area burns, a small clinical trial shows that taking a collagen-based supplement providing collagen peptides (Amutiya, Qom) 36 grams daily for 4 weeks improves wound healing when compared with taking an isocaloric supplement containing the same amount of soy protein. Complete wound healing occurred in 50% and 100% of patients taking collagen for 2 and 4 weeks, respectively, compared with 7% and 40% of those taking the isocaloric product. The duration of hospital stay was not significantly different between the two groups (104642). A small clinical study in hospitalized adults with 20-45% body surface area 2nd or 3rd degree burns shows that consuming a beverage containing collagen peptides 40 grams daily for 4 weeks shortens the time to wound healing, improves scar scores, and reduces the duration of hospital stays but does not limit wound infections when compared with placebo. Adding fish oil 3 grams daily did not further improve outcomes (110667).
• Brittle nails. One small clinical study suggests that oral collagen peptides may improve nail health in people with brittle nails. Details: A small clinical study shows that taking a specific porcine type I collagen peptide product (VERISOL, Gelita AG) 2.5 grams daily for 6 months improves overall symptoms of brittle nail syndrome, increases nail growth rate by 12%, and reduces broken nail frequency by 42% when compared with baseline (101606). This study was limited by its small size and lack of a comparator group.
• Cellulite. One small clinical study suggests that oral collagen peptides may reduce cellulite. Details: In people with cellulite, a small clinical study shows that taking specific collagen peptides (VERISOL by Gelita AG) 2.5 grams daily for 6 months seems to reduce cellulite, skin waviness, and dermal density by a small amount when compared with placebo (101619).
• Cognitive function. It is unclear if oral collagen peptides are beneficial for improving memory. Details: In healthy adults, preliminary clinical research shows that taking collagen peptides 5 grams daily for 4 weeks improves some measures of memory and verbal learning when compared to baseline (104643). This study was limited by its small size and lack of a comparator group.
• Dermatoporosis. One small clinical study suggests that using oral or topical collagen peptides does not improve this condition. Details: A small clinical study in post-menopausal patients aged 70 years on average with mild dermatoporosis shows that taking collagen peptides 5 grams daily, applying a collagen peptides 2.5% serum 3 pumps nightly to each forearm, or using these in combination for 6 months does not improve skin lesions, epidermal thickness, collagen or elastin density, or patient perception of skin improvement when compared with placebo (110731). However, it is unclear if these results apply to patients with more severe dermatoporosis.
• Diabetes. Some preliminary clinical research suggests that oral collagen peptides might have a small effect on glycemic indices. Details: Preliminary clinical research in patients with type 2 diabetes shows that taking fish-derived collagen peptides 6.5 grams orally twice daily for 3 months, in addition to treatment with antidiabetes drugs, may modestly reduce levels of fasting blood glucose, glycated hemoglobin, and fasting blood insulin and may increase levels of insulin sensitivity when compared with antidiabetes drugs and placebo (101626,101627).
• Erythema. It is unclear if oral collagen peptides are beneficial for erythema. Details: A moderate-sized clinical study in adults with dry and wrinkled eye skin shows that taking low-molecular weight collagen peptides (GPVGPS Collagen, Daehan Chemtech) 2000 mg daily for 12 weeks reduces erythema index when compared with placebo (112458).
• Exercise-induced gastrointestinal (GI) symptoms. It is unclear if oral collagen peptides prevent GI symptoms due to exercise. Details: A small crossover study in moderately well-trained young adults shows that taking collagen peptides 10 grams daily for 7 days prior to rigorous treadmill exercise does not limit GI symptoms but may attenuate some markers of GI distress when compared with placebo (110665).
• Exercise-induced muscle soreness. It is unclear if oral collagen peptides prevent muscle soreness after exercise. Details: Preliminary clinical research in a small number of healthy, recreationally active adults shows that taking collagen peptides (Peptan, Rousselot BVBA, Collagen Peptides, Vital Proteins) 10-15 grams twice daily, starting 7 days prior to strenuous exercise and continuing for 2-5 days after, does not reduce muscle soreness when compared with placebo (100700,104648). However, there was a small benefit on the recovery of countermovement jump ability within 24 hours (104648). Furthermore, another small clinical study in adults unaccustomed to exercise shows that taking collagen peptides 10 grams daily for 33 days modestly reduces muscle soreness and fatigue immediately after the exercise load, but not 2 hours after exercise or the next morning, when compared with placebo (111639). Also, a small clinical study in active middle-aged adults shows that taking specific collagen peptides (SOLUGEL Collagen Peptides, PB Leiner) 10 grams daily for 6 months improves pain in those who exercise frequently (>188 minutes weekly) when compared with placebo. However, collagen peptides do not seem to improve pain in low frequency exercisers (<188 minutes weekly) (112455). Collagen peptides have also been evaluated in combination with other ingredients. One preliminary clinical study in healthy, recreationally active adults shows that taking a specific product (BioCell Collagen, BioCell Technology, LLC) containing collagen peptides from chicken collagen type II, hyaluronic acid, and chondroitin sulfate 1.5 grams twice daily for 6 weeks prior to two bouts of intense resistance exercise attenuates increases in biomarkers of muscle damage and decreases delayed onset muscle soreness when compared with placebo (96301). It is unclear if these benefits are due to collagen peptides, other ingredients or the combination.
• Gingivitis. It is unclear if oral collagen peptides are beneficial for patients with gingivitis. Details: A small clinical study in patients with mild-to-moderate chronic gingivitis shows that taking a specific collagen peptide product (Verisol B, Gelita AG) 5 grams daily for 90 days following mechanical plaque removal reduces bleeding and inflammation but does not improve plaque scores when compared with placebo (110666).
• Hypertension. Limited research suggests that oral collagen peptides may lower systolic or diastolic blood pressure. However, results are inconsistent. Details: One preliminary clinical study in patients with hypertension and type 2 diabetes shows that taking fish-derived collagen peptides 6.5 grams twice daily for 3 months modestly reduces diastolic, but not systolic, blood pressure when compared with placebo (101626). Another small clinical study in patients with mildly elevated blood pressure shows that taking a test food containing chicken leg-derived collagen peptides 2.9 grams daily for 12 weeks lowers systolic, but not diastolic, blood pressure when compared with placebo (101610). An additional small clinical study in patients with mild hypertension shows that taking chicken leg-derived collagen peptides 5.2 grams daily 4 weeks reduces systolic blood pressure by 12 mmHg when compared with baseline (101618). This study was limited by its small size and lack of a comparator group. The reasons for conflicting data are unclear.
• Insomnia. It is unclear if oral collagen peptides are beneficial for insomnia. Details: A very small clinical study in physically active males with difficulty sleeping shows that taking collagen peptides 15 grams before bedtime for 7 nights reduces the frequency of nocturnal awakenings and improves cognitive accuracy but does not improve objective measures of total sleep time, latency, efficiency, stage changes, waking after sleep onset, other cognitive function measures, or subjective measures of sleepiness, fatigue, and sleep quality when compared with placebo (112459).
• Joint pain. Most research shows that oral collagen peptides might moderately reduce joint pain in young athletes. However, evidence in elderly patients is conflicting. Details: Preliminary clinical research in student athletes with joint pain shows that taking a specific collagen peptide product (FORTIGEL, Gelita AG) 10 grams in 25 mL of liquid daily for 24 weeks modestly improves pain during movement and at rest when compared with placebo (101601). Other clinical research in young adults exercising or participating in sports at least 3 hours weekly with activity-related knee pain shows that taking this same product 5 grams daily for 12 weeks reduces pain intensity during activity by 38% to 41%, compared with a 26% to 28% reduction in those taking placebo. However, there was no improvement in pain at rest or after the activity when compared with placebo (97623,107454). Furthermore, it is not clear if these effects are clinically significant. Research on the use of collagen peptides in older patients is conflicting. A small clinical study in otherwise healthy patients aged 40-65 years with joint discomfort shows that taking a specific collagen peptides product (AVC-H2, Avicenna) 1.25 grams twice daily for 8 weeks improves overall Western Ontario and McMaster Universities Osteoarthritis (WOMAC) scores by 37% at 4 weeks, compared with 14% in those receiving placebo. However, this difference in improvement was no longer significant at 8 weeks. Collagen peptides also improved the physical activity and stiffness subdomains, but not the pain subdomain, at 4 and 8 weeks when compared with placebo (107455). A larger clinical study in patients 50 years or older with general joint pain shows that taking a specific collagen peptides product (Genacol) 1200 mg daily for 6 months does not reduce pain or improve function when compared with placebo (97657). However, collagen peptides used in combination with other ingredients have shown benefit. Preliminary clinical research in patients 51-70 years of age shows that taking a specific combination product (Gold Collagen Active, Minerva Research Labs) containing fish collagen peptides 4 grams, glucosamine hydrochloride 1000 mg, chondroitin sulfate 500 mg, L-carnitine 200 mg, and other ingredients daily for 90 days reduces joint pain by 43% when compared with baseline, while patients taking placebo saw negligible improvement in pain. A greater percentage of patients taking this product also perceived improvements in joint discomfort, flexibility, mobility, and rigidity when compared with placebo (100703). It is unclear if these effects are due to collagen peptides, other ingredients, or the combination.
• Obesity. It is unclear if oral collagen peptides are beneficial for weight loss. Details: A preliminary clinical study in adults with overweight shows that taking skate skin-derived collagen peptides 2 grams daily for 12 weeks modestly reduces body fat mass by 1.2 kg, compared with an increase of 0.3 kg in the placebo group (101621). It is unclear if collagen peptides improve weight loss or reduce body fat mass in the long-term.
• Osteoarthritis. Most research suggests that oral collagen peptides improve pain in patients with knee osteoarthritis; however, any improvement is modest and may not be considered clinically significant. Details: A meta-analysis of 3 clinical studies, all of which are included below, in adults with knee osteoarthritis shows that taking collagen peptides or hydrolyzed collagen reduces pain when compared with placebo (112456). Clinical research shows that taking specific collagen peptides (Colnatur, Protein SA) 10 grams daily for 5 months increases the number of patients who experience at least a 30% improvement in pain by approximately 42% when compared with placebo. However, there is no difference between groups when the Western Ontario and McMaster Universities (WOMAC) scale is used. Patients with the greatest joint deterioration at baseline, as well as those with the lowest dietary meat intake, seemed most likely to experience benefit from collagen peptides (97635). Another small clinical study shows that taking collagen peptides isolated from pork skin and bovine bone (Nitta Gelatin Inc.) 5 grams dissolved in 250 mL water or milk twice daily after food for 13 weeks modestly improves pain when compared with placebo (101611). Another small clinical study in patients over 40 years old shows that taking collagen peptides (Colatech) 10 grams daily for 90 days reduces pain by about 2 points on a 100-point scale, compared with a 0.9-point reduction with glucosamine sulfate 1.5 grams. Ibuprofen use was not affected (101622). One multicenter clinical study shows that taking collagen peptides 10 grams daily for 6 months does not relieve pain or improve joint function when compared with placebo, although a trend towards reduced pain and improved joint function was observed in patients with severe symptoms at baseline (7704). Collagen peptides have also been evaluated in combination with other ingredients. Clinical research in patients with osteoarthritis of the knee, hip, or hand shows that taking a specific product (BioCell Collagen, BioCell Technology, LLC) containing collagen peptides from chicken collagen type II, hyaluronic acid, and chondroitin sulfate 1 gram twice daily for up to 10 weeks reduces pain and the need for rescue analgesics and increases physical activity when compared with placebo (28678,28680). Similarly, a moderate-size clinical study in patients aged 45-75 years with mild to moderate knee osteoarthritis undergoing resistance exercise twice weekly shows that taking a specific product (Suntory Beverage and Food Asia) containing collagen peptides from chicken collagen type II, hyaluronic acid, and chondroitin sulfate 2 grams daily for 24 weeks does not improve WOMAC scores when compared with glucosamine 1.5 grams daily or placebo, but may modestly improve pain scores when compared with placebo. However, the use of rescue analgesics was not assessed. Adding essence of chicken 5.81 grams daily to collagen peptides did not improve WOMAC or pain scores (110670). Also, preliminary clinical research in patients with knee osteoarthrosis shows that taking a specific product (Ialoral 1500, PharmaSuisse Laboratories Srl) containing collagen peptides, chondroitin sulfate, hyaluronic acid, and keratin peptides for 4 weeks improves pain and function by a moderate amount when compared with baseline (104645). However, the validity of these findings is limited by the lack of statistical comparison to the control group. It is unclear if these effects are due to collagen peptides, other ingredients, or the combination.
• Osteopenia. It is unclear if oral collagen peptides prevent loss of bone mineral density (BMD) in postmenopausal adults. Details: A large clinical study in patients with reduced BMD after menopause shows that taking specific collagen peptides (Fortibone, Gelita AG) 5 grams daily for 12 months increases BMD of the spine and the femoral neck by 3% and 7%, respectively, compared with losses of 1% with placebo (101609). In a very small observational extension of this study, BMD continued to increase over an additional 4 years when compared with baseline. However, the validity of these findings is limited by the lack of a comparator group (107340). Collagen peptides have also been evaluated in combination with calcium and vitamin D. In patients with osteopenia after menopause, a small clinical study shows that taking collagen peptides calcium chelate 5 grams, containing elemental calcium 500 mg and vitamin D3 200 IU, daily for 12 months does not affect total hip, total body, or vertebral BMD when compared with calcium 500 mg and vitamin D 200 IU (101604). The validity of these results is limited by a high dropout rate and insufficient power to detect smaller effects. Conversely, another small study in this population shows that taking specific collagen peptides (Fortibone, Gelita AG) in combination with elemental calcium (as calcium lactate) 500 mg and vitamin D3 400 IU daily for 12 months improves trabecular bone mineral content, trabecular volumetric BMD, and cortical volumetric BMD, but not cortical bone mineral content, when compared with a combination tablet containing equivalent doses of elemental calcium (as calcium carbonate) and vitamin D (107453). It is unclear if these effects are due to collagen peptides, other ingredients, or the combination.
• Osteoporosis. It is unclear if oral collagen peptides improve bone mineral density (BMD) in adults with osteoporosis after menopause. Details: In patients with osteoporosis after menopause, clinical research shows that taking collagen peptides 10 grams daily in addition to twice weekly intramuscular calcitonin for 6 months does not improve BMD in the forearm when compared with calcitonin alone (104649). It is unclear if supplementation with collagen peptides improves BMD in the femoral neck or lumbar spine.
• Pressure ulcers. Oral collagen peptides might help to improve ulcer size and healing. Details: A small clinical study in patients with Stage II, III, or IV pressure ulcers shows that taking collagen peptides 5 grams orally three times daily for 8 weeks in addition to standard care improves ulcer size and exudate when compared with placebo and standard care (101612). This study was limited because it only used one scale to assess healing of the pressure ulcer. Another small clinical study in patients with stage II or III pressure ulcers shows that receiving standard care and collagen peptides with high levels of prolyl-hydroxyproline 5 grams twice daily for 16 weeks improves ulcer exudate, healing, and wound size when compared with standard care plus placebo (101620).
• Sarcopenia. Oral collagen peptides might help to increase fat-free mass. However, it is unclear if collagen peptides are more beneficial than other types of protein. Details: A small clinical study in elderly males with sarcopenia shows that taking collagen peptides from type I collagen 15 grams daily for 12 weeks along with three resistance training sessions weekly modestly increases fat-free mass and power when compared with resistance training and placebo (101624). It is unclear if supplementation with collagen peptides is more beneficial than supplementation with protein.
• Sprains. It is unclear if oral collagen peptides improve ankle instability after a previous sprain. Details: A small clinical study in athletes with chronic ankle instability from an ankle sprain shows that taking collagen peptides 5 grams daily for 6 months improves subjective ankle instability when compared with placebo. However, ankle stiffness, which is a more objective measure of ankle instability, is not improved when compared with placebo (101603).
• Tendinopathy. It is unclear if oral collagen peptides improve tendon pain. Details: A small clinical study in patients with Achilles tendinopathy shows that taking a specific collagen peptides supplement (TENDOFORTE, Gelita AG) 2.5 grams daily for 3 months in addition to a calf-strengthening program improves pain when compared with baseline (101615). The validity of this finding is limited by the lack of a comparator group.
• Wound healing. It is unclear if oral collagen peptides improve wound healing. Details: A small clinical study in healthy volunteers with wounds after photothermolysis shows that taking collagen peptides 3 grams daily for 4 weeks improves erythema, skin hydration, and skin elasticity when compared with placebo (101599). This study was limited by small size, short duration, and no direct measurement of wound healing or scar formation.
• Wrinkled skin. Some small clinical studies suggest that oral collagen peptides might help to reduce lines and wrinkles from sun damage. Details: Preliminary clinical research in females with photodamaged skin shows that taking a specific low molecular weight collagen peptide product (Evercollagen, Newtree Co.) 1000 mg daily for 12 weeks modestly improves most measures of skin wrinkling, hydration, and elasticity when compared with placebo. This specific collagen peptide product is standardized to contain more than 15% glycine-containing tripeptides, including 3% glycyl-prolyl-hydroxyproline (100702). Another moderate-sized clinical study in adults with dry and wrinkled eye skin shows that taking low-molecular weight collagen peptides (GPVGPS Collagen, Daehan Chemtech) 2000 mg daily for 12 weeks reduces skin wrinkling parameters including facial skin roughness, peak-to-valley values, maximum wrinkle height, and eye wrinkle volume and improves skin hydration and skin elasticity when compared with placebo. However, there was no improvement in maximum wrinkle depth (112458). Another preliminary clinical study shows that taking a specific combination product (BioCell Collagen, BioCell Technology, LLC) containing collagen peptides from chicken collagen type II 600 mg, low molecular weight hyaluronic acid 100 mg, and chondroitin sulfate 200 mg daily for 12 weeks reduces lines and wrinkles associated with both natural aging and photoaging by about 13% when compared to baseline (28681). This study was limited by the lack of a comparator group. Additionally, it is unclear if these effects are due to collagen peptides, other ingredients, or the combination. More evidence is needed to rate collagen peptides for these uses.

(Read more about COLLAGEN PEPTIDES)

POSSIBLY EFFECTIVE

• Athletic performance. Most available research suggests that oral tart cherry modestly improves muscular strength and endurance when compared with control. However, most studies are limited by a high risk of selection bias. Details: A meta-analysis of 14 small studies involving a total of 303 trained athletes and untrained healthy adults shows that tart cherry might modestly improve recovery of muscular strength and power when compared with control. Also, some subgroup analyses show that tart cherry may improve recovery of jump height and sprint time when compared with control (105629). In another meta-analysis of 10 studies involving 147 marathon runners, cyclists, or triathletes at various levels of training, taking tart cherry juice concentrate or powder 1.5 hours before exercise, or for up to 7 days prior to exercise, seems to improve exercise endurance, as measured by the time to complete an exercise trial, when compared with control (102340). However, both analyses have a high risk of selection bias and some analyses have high heterogeneity. Specific products assessed in the meta-analyses include tart cherry juice (CherryActive, Active Edge Nutrition) 60 mL, 90 minutes prior exercise (98699); a specific tart cherry concentrate (CherryActive, Active Edge Nutrition) 30 mL twice daily for 8 days (93149); and a specific freeze-dried tart cherry supplement (CherryPURE, Shoreline Fruit LLC) 480 mg daily 7 days before, on the day of, and 2 days after exercise (93158).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aromatase inhibitor-induced arthralgia. It is unclear if oral tart cherry is beneficial in patients with aromatase inhibitor-induced arthralgia (AIIA). Details: Preliminary clinical research in a small group of females with non-metastatic, hormone-receptor positive breast cancer and AIIA after taking aromatase inhibitors for at least 4 weeks shows that taking tart cherry juice concentrate 30 mL daily for 6 weeks reduces pain scores on a visual analog scale by about 35%, compared with 1% in those taking placebo (109657).
• Attention deficit-hyperactivity disorder (ADHD). It is unclear if oral tart cherry juice is beneficial in children with ADHD. Details: A small clinical study in children and adolescents aged 6 to 18 years with ADHD shows that consuming tart cherry juice concentrate 75 mL twice daily for 2 weeks with standard treatment does not improve ADHD symptoms including cognitive impairment, hyperactivity, impulsivity, or oppositional behavior when compared with placebo (112815).
• Cognitive function. It is unclear if oral tart cherry improves cognitive function. Details: Preliminary clinical research in healthy, middle-aged adults shows that taking tart cherry juice concentrate 30 mL orally twice daily for 3 months reduces mental fatigue and improves performance on tests evaluating sustained attention, psychomotor speed, and alertness when compared with placebo. However, it does not affect sleep quality or cerebral blood flow (109655).
• Exercise-induced muscle soreness. Research on the use of oral tart cherry juice or supplements for the reduction of exercise-induced muscle soreness is conflicting. Details: A meta-analysis of 12 small studies in trained athletes and untrained healthy adults shows that tart cherry might modestly attenuate delayed muscle soreness after exercise involving maximal muscle contractions or maximal effort sprints when compared with control. However, tart cherry juice seems to be no better than placebo for improving delayed muscle soreness after prolonged aerobic exercise (105629). These findings are limited by a high risk of selection bias, high heterogeneity, and imprecision. Some products assessed in the meta-analysis include a specific Montmorency tart cherry concentrate (Holland & Barrett Ltd.) 30 mL twice daily for 5 days before, on the day of, and for 2 days after intermittent sprint exercises (102341); a specific freeze-dried tart cherry supplement (CherryPURE, Shoreline Fruit LLC) 480 mg daily for 7 days before, on the day of, and 2 days after running a half-marathon or doing back squats (93157,93158); a specific Montmorency tart cherry juice concentrate (CherryActive, Active Edge Nutrition) 30 mL diluted in water and taken twice daily for 8 days (93149,93151,101880,102344); and a specific juice (Sour cherry juice, Cherrypharm Inc.) containing 90% tart cherry juice and 10% apple juice as a sweetener, twice daily (93152,93154). Some individual clinical studies have yielded mixed findings. One clinical study in professional rugby players shows that taking a Montmorency tart cherry juice concentrate gel, 30 mL (equivalent to 100 cherries) twice daily for 2 days before, on the day of, and for 2 days after a match does not improve muscle soreness when compared with placebo (102339). Similarly, in male professional soccer players, taking tart cherry juice, 60 mL before and after a 90-minute match and then 12 and 36 hours later, does not improve subjective muscle soreness when compared with placebo (102342). Also, a small study in healthy males shows that taking a specific tart cherry supplement (Tart Cherry Extract Powder NordicCherry, Specnova, LLC.) 500 mg daily for 7 days prior to performing resistance exercise does not reduce muscle soreness when compared with placebo (105631). In contrast, a small clinical study in recreational long-distance runners shows that drinking a specific tart cherry juice (Cherrish, Cherrish Corp.) 10.5 ounces twice daily for 7 days prior to a long-distance race decreases post-race muscle pain by around 65% when compared with placebo (93156). Reasons for the discrepancies may include differences in tart cherry products, the small number of subjects, and heterogeneity in study populations and evaluated endpoints. In some studies, the subjects' normal diets were continued during the study, whereas in others, a reduced polyphenol diet was consumed for the duration of the study (102342,105629).
• Exercise-induced respiratory infections. It is unclear if oral tart cherry juice reduces the risk of exercise-induced respiratory infections. Details: A small clinical study in recreational athletes shows that drinking a specific juice blend (Sour cherry juice, Cherrypharm Inc.), containing 90% tart cherry juice and 10% apple juice as a sweetener, 8 ounces twice daily for 5 days before, on the day of, and 2 days after running a marathon, decreases the risk for upper respiratory tract symptoms such as cough, sore throat, congestion, and sneezing when compared with placebo (93168).
• Fibromyalgia. It is unclear if oral tart cherry improves symptoms in patients with fibromyalgia. Details: A very small clinical study in females with fibromyalgia participating in an eccentric exercise program shows that taking a specific tart cherry concentrate (Cherrish, Cherrish Corp.) 10.5 ounces twice daily for 14 days does not improve pain or muscle strength when compared with placebo (93192).
• Gout. It is unclear if oral tart cherry juice reduces symptoms of gout; research is conflicting. Details: Preliminary clinical research shows that tart cherry juice lowers serum urate and increases urinary urate excretion in healthy people, as well as people with hyperuricemia that has not progressed to gout (93166,102338). However, in patients with gout, taking Montmorency tart cherry juice concentrate (Cherryvite) in doses of 7.5-30 mL twice daily for 28 days does not affect urate excretion or the frequency of gout flares (102343). A small, unblinded clinical study in adults with chronic gout shows that taking a combination product (GoutFighter, MaxBiocare Pty Ltd.) containing tart cherry fruit extract 100 mg, celery seed extract 300 mg, devil's claw tuber extract 150 mg, folic acid 90 mcg, potassium citrate 50 mg, and ascorbic acid 50 mg orally, as 2 tablets twice daily for 45 days, modestly reduces mean serum uric acid levels and reduces perceived pain and frequency of joint swelling when compared to baseline (106488). The validity of these findings is limited by the lack of a comparator group. Additionally, it is unclear if any effects are due to tart cherry, other ingredients, or the combination.
• Hypertension. It is unclear if oral tart cherry juice reduces blood pressure; research is conflicting. Details: A very small clinical study in males with mild hypertension shows that taking 60 mL of a specific tart cherry concentrate (CherryActive, Active Edge Nutrition) modestly decreases systolic, but not diastolic, blood pressure 1-3 hours after consumption when compared with placebo (93155). This finding is limited by the small study size and the use of a single dose. Another small study in healthy adults without hypertension shows that drinking 30 mL of Montmorency tart cherry concentrate (Cherry Marketing Institute) diluted in 240 mL of water daily for 3 months does not reduce blood pressure when compared with baseline or placebo (105633).
• Insomnia. Some small clinical studies suggest that oral tart cherry juice may modestly improve sleep and reduce insomnia. This effect might be due to the melatonin content in tart cherry juice. However, the evidence is conflicting. Details: A small clinical study in healthy adults less than 40 years of age shows that consuming a specific tart cherry juice concentrate (CherryActive, Active Edge Nutrition) 30 mL standardized to contain 1.42 mcg/mL of melatonin twice daily for 7 days modestly increases total sleep time and efficiency when compared with placebo (17199). Another small clinical study in adults aged 65 years and older with chronic insomnia shows that drinking a specific juice blend (Sour cherry juice, Cherrypharm Inc.), containing 90% tart cherry juice and 10% apple juice as a sweetener, 8 ounces twice daily for 14 days, modestly improves insomnia severity, but not sleep latency, when compared with placebo (17403). However, another very small clinical study in healthy adults shows that taking Montmorency tart cherry juice 240 mL twice daily or powdered Montmorency tart cherry capsules 1000 mg daily for 30 days does not improve sleep quality, sleep time, or serum melatonin concentration when compared with placebo (112813). The effects of tart cherry on sleep measures have also been evaluated in combination with other ingredients. A very small crossover study in healthy adults without a sleep disorder shows that taking a combination product containing tart cherry powder 220 mg, tryptophan, glycine, magnesium, and L-theanine 2 hours before bedtime for 3 nights decreases the time to fall asleep by about 24 minutes, increases total sleep duration by about 22 minutes, improves sleep efficiency, and reduces morning sleepiness, but does not improve the total time in bed or wakefulness after falling asleep when compared with placebo (111184). It is unclear if these effects are due to tart cherry, other ingredients, or the combination.
• Metabolic syndrome. Oral tart cherry juice does not seem to improve cardiovascular or metabolic biomarkers in patients at risk for or with metabolic syndrome. Details: Two meta-analyses of small, moderate-quality clinical studies in healthy adults, patients with metabolic syndrome, or those with risk factors for metabolic syndrome, that include many of the same studies, show that drinking tart cherry juice 30-480 mL daily for 1-12 weeks does not improve fasting blood glucose, insulin levels, lipid profiles, blood pressure, body weight, body mass index, fat mass, percentage body fat, or waist circumference when compared with placebo (112812,112814).
• Osteoarthritis. It is unclear if oral tart cherry juice is beneficial in patients with osteoarthritis. Details: A small clinical study in patients with osteoarthritis shows that drinking a specific juice blend (Sour cherry juice, Cherrypharm Inc.) containing 90% tart cherry juice and 10% apple juice as a sweetener, 8 ounces twice daily for 6 weeks, does not improve pain, stiffness, function, walking speed, or acetaminophen use when compared with placebo (93160). The validity of this finding is limited because the trial was not adequately powered to detect small differences between groups. More evidence is needed to rate tart cherry for these uses.

(Read more about TART CHERRY)

LIKELY SAFE ...when used orally and appropriately, short-term. Andrographis has been used with apparent safety in doses of up to 6 grams daily for up to 7 days. Andrographis extract has been used with apparent safety at doses of up to 340 mg daily for up to 12 months, 600 mg daily for up to 3 months, or 1200 mg daily for up to 8 weeks (2748,31220,31223,31231,91838,91839,101116). Andrographolide, a constituent of andrographis, has been used with apparent safety at a dose of 280 mg daily for 24 months (104821). A specific combination product containing andrographis extract 178-206 mg and eleuthero (Kan Jang, Swedish Herbal Institute) has been taken three times daily with apparent safety for up to 4-7 days (2744,2748,2773,2774,10441,10795,13016).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. Andrographis, in combination with other herbs, has been used with apparent safety in clinical trials at doses up to 48 mg daily in children 3-15 years of age for up to one month (12381,12382).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Andrographis is thought to have abortifacient effects (12); avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about ANDROGRAPHIS)

POSSIBLY SAFE ...when used orally and appropriately, short-term. Preparations of Cissus quadrangularis dried herb have been used with apparent safety in doses up to 1600 mg for 24 weeks (93634,95923,112140). An Ayurvedic preparation of the dried herb has been used with apparent safety in doses of 6-10 grams daily for 4-6 weeks (95921,95922). Some research shows that a specific Cissus quadrangularis product (SuperCissus, USPlabs) can be used safely in a dose of 3.2 grams daily for up to 8 weeks (93633). Other research shows that another specific Cissus quadrangularis extract (CQR-300; Gateway Health Alliance) has been used with apparent safety in a dose of 300 mg daily for up to 10 weeks (15609,16457,93637,99257).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about CISSUS QUADRANGULARIS)

POSSIBLY SAFE ...when used orally and appropriately, short-term. Collagen peptides have been used with apparent safety at doses up to 10 grams daily for up to 6 months and in doses up to 40 grams daily for up to 4 weeks (97632,97635,101615,101621,104638,104643,104644,104647,101622,110667). PREGNANCY &

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about COLLAGEN PEPTIDES)

LIKELY SAFE ...when the fruit is used in amounts commonly found in foods. ...when tart cherry fruit, fruit juice, or fruit juice concentrate is used orally in supplemental amounts for up to 3 months (17403,93149,93151,93152,93153,93154,93156,93157,93158,93160)(93161,93168,93179,105633).

POSSIBLY SAFE ...when tart cherry fruit extract or powder is used orally, short term. Cherry fruit extract or freeze-dried cherry powder up to 500 mg daily for up 7 days has been used with apparent safety (93157,93158,105631). There is insufficient reliable information available about the safety of tart cherry stem when used orally.

PREGNANCY AND LACTATION: LIKELY SAFE
when the fruit is consumed in typical food amounts. There is insufficient reliable information available about the safety of tart cherry fruit or stem when used in medicinal amounts; avoid using.

(Read more about TART CHERRY)

ACECLOFENAC Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, andrographis extract might increase the maximum concentration and decrease the area under the curve of aceclofenac. The clinical significance of these changes is unclear.  Details Animal research suggests that andrographis extract taken orally increases the maximum concentration and decreases the area under the curve of aceclofenac (112916).

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, andrographis might increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.  Details Animal and laboratory studies suggest that andrographis has antiplatelet effects (2758,2759).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, andrographis might increase the risk of hypotension when used with antihypertensive drugs.  Details Animal research suggests that andrographis has hypotensive effects (2755,2760).

CELECOXIB (Celebrex) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, andrographis extract might increase the maximum concentration and time to peak concentration of celecoxib. The clinical significance of these changes is unclear.  Details Animal research suggests that andrographis extract taken orally increases the maximum concentration and time to peak concentration of celecoxib but does not appear to impact the area under the curve (112916).

ETORICOXIB (Arcoxia) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, andrographis might decrease the absorption of etoricoxib, although the clinical significance is unclear.  Details Animal research shows that andrographis extract, or the constituent andrographolide, taken orally with etoricoxib decreases the bioavailability of etoricoxib. However, this reduced bioavailability is not correlated with a reduction in the anti-inflammatory effects of etoricoxib in arthritic mice models (91837). The clinical significance of this interaction is unclear.

GLIPIZIDE (Glucotrol) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, andrographis extract might increase the maximum concentration and area under the curve of glipizide; however, opposite effects are seen with the constituent, andrographolide. The clinical significance of this interaction is unclear.  Details Animal research suggests that andrographis extract taken orally with glipizide in diabetes-induced rats increases the maximum concentration and area under the curve of glipizide. However, the opposite effect is seen with the constituent, andrographolide, in which the maximum concentration and area under the curve are decreased when taken with glipizide (112917).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, andrographis might interfere with the effects of immunosuppressive drugs.  Details Laboratory research suggests that andrographolide has immunostimulant activity (2766).

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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Cissus quadrangularis might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Small clinical studies suggest that Cissus quadrangularis might reduce fasting blood glucose in individuals with overweight or obesity (16457,99257).

(Read more about CISSUS QUADRANGULARIS)

(Read more about COLLAGEN PEPTIDES)

(Read more about TART CHERRY)

General ...Orally, andrographis is generally well tolerated. Adverse effects are more likely when doses reach or exceed 5-10 mg/kg of andrographolide content and when treatment duration exceeds 14 days.
Most Common Adverse Effects:
Orally: Abdominal discomfort, altered taste, diarrhea, dizziness, fatigue, headache, nausea and vomiting, pruritus, rash, and urticaria.
Serious Adverse Effects (Rare):
Orally: Severe allergic reactions, including anaphylaxis.

Cardiovascular ...Orally, andrographis has been reported to cause vasculitis, edema, and increased sweating (12380,13016,91841).

Dermatologic ...Orally, andrographis has been frequently reported to cause maculopapular, erythematous rash, pruritus, and urticaria (31223,31222,31233,12380,31231,31220,13016,91838,91841,104821)(107783,112921). Andrographis consumption has also been reported to cause angioedema, exfoliative dermatitis, skin exfoliation, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, bullous eruption, fixed eruption, stomatitis, allergic purpura, flushing, and swelling (91841).
Parenterally, there have been reports of maculopapular rash, urticaria, pruritus, and flushing with the use of andrographolide derivative injections; about one-third of patients experienced skin or subcutaneous reactions (112921).

Gastrointestinal ...Orally, andrographis has been reported to cause nausea, vomiting, diarrhea, dyspepsia, flatulence, altered or metallic taste, and abdominal discomfort (6767,31213,2748,13016,31220,31222,91841,104821,107783,112921). Andrographis intake has also been reported to cause epigastric pain, ulcerative stomatitis, melena, dry mouth, and dry lips (31213,10795,13016,91841).
Parenterally, there have been reports of diarrhea, nausea, vomiting, and abdominal discomfort with the use of andrographolide derivative injections; over 40% of patients experienced gastrointestinal events (112921).

Genitourinary ...Orally, there is one case report of increased urinary frequency associated with andrographis use (91841)

Hematologic ...Orally, there is one case report of epistaxis (nosebleed) associated with andrographis use (31222).

Hepatic ...Orally, there is one case report of hepatitis associated with andrographis use (91841).

Immunologic ...Orally, andrographis has been reported to cause anaphylactic shock in 2 cases with determined causality, and 7 cases with probable causality. Anaphylactic shock developed in 5 minutes to one day after oral intake, and included symptoms such as hypotension, chest pain, urticaria, angioedema, wheezing, and tachycardia (91841). Additionally, andrographis intake has been associated with cases of eosinophilia and fever (91841,107783). High doses of the andrographolide constituent (5-10 mg/kg daily) have been associated with two cases of lymphadenopathy and three cases of lymph node pain (6767).
Parenterally, there have been 97 cases reporting severe or life-threatening anaphylaxis after andrographolide derivative injections, 3 of which resulted in death (112921).

Musculoskeletal ...Orally, andrographis has been associated with case reports of pain, muscle weakness, cramps, and paralysis (31220,91841,107783).

Neurologic/CNS ...Orally, andrographis has been reported to cause headache, fatigue, anorexia, somnolence, insomnia, lethargy, malaise, and drowsiness (2748,5784,6767,10795,12380,13016,31220,31213,31222,91841,107783). Headache and fatigue occurred more often with high doses of the andrographolide constituent (5-10 mg/kg daily) in one clinical trial (6767).

Pulmonary/Respiratory ...Orally, andrographis has been reported to cause dyspnea, coughing, bronchospasm, increased sputum, and nasal congestion (10795,13016,31213,91841,107783).

(Read more about ANDROGRAPHIS)

General ...Orally, Cissus quadrangularis seems to be well tolerated.

Gastrointestinal ...Orally, Cissus quadrangularis has been reported to cause flatulence (15608,16457), diarrhea (15608,112140), gastritis (43204), and dry mouth (15608). However, the rates of these adverse effects are similar to or lower than that observed with placebo (15608,16457,43204,112140).

Neurologic/CNS ...Orally, Cissus quadrangularis has been reported to cause headache and insomnia. However, the rates of these adverse effects are similar to or lower than that observed with placebo (15608,16457).

(Read more about CISSUS QUADRANGULARIS)

General ...Orally, collagen peptides seem to be well tolerated.

Dermatologic ...Orally, a case of a mild skin rash has been reported for a patient who used a specific collagen peptide-containing product (BioCell Collagen) (28680).

Gastrointestinal ...Orally, collagen peptides may cause nausea, dyspepsia, diarrhea, and flatulence, but these adverse effects are rare (101622,104639).

(Read more about COLLAGEN PEPTIDES)

General ...Tart cherry is generally well tolerated when consumed as whole fruit, juice concentrate, or seed extracts.
Most Common Adverse Effects:
Orally: Abdominal pain, asthenia, gastrointestinal upset, loose stools.

Endocrine ...One case of hyperglycemia after drinking a specific blend of tart cherry and apple juices ) has been reported (93160).

Gastrointestinal ...In a clinical study, 29% of children who consumed 75 mL of tart cherry juice concentrate twice daily for 2 weeks reported abdominal pain (112815). Two cases of loose stools after consumption of 90 whole tart cherries, and one case of gastrointestinal disturbance after drinking 10.5 ounces of tart cherry concentrate (Cherrish, Cherrish Corp.) twice daily for 14 days have been reported (93186,93192). One case of gastrointestinal symptoms after drinking a specific blend of tart cherry and apple juice (Sour cherry juice, Cherrypharm Inc.) has been reported (93160).

Immunologic ...One case of a skin reaction possibly due to cherry allergy after drinking a specific blend of tart cherry and apple juice ) has been reported (93160).

Musculoskeletal ...In a clinical study, 31% of children who consumed tart cherry juice concentrate 75 mLl twice daily for 2 weeks reported asthenia (112815).

(Read more about TART CHERRY)